Our laboratory has continued investigation of photodynamic therapy for the treatment of thoracic malignancies by sensitization of, malignant cells with dihematoporphyrin ether followed by illumination by 630 nM light. Since October 1989 we have established the sensitivity of different lung cancer lines in vitro. We have found minor variations in vitro as far as phototherapy sensitivity. We have characterized these changes with regard to dihematoporphyrin ether content, cell size, cell volume, cell protein as well as plating efficiency. We have published investigations concerning the treatment of murine macrophages with tumor necrosis factor and have revealed that photodynamic therapy stimulates, these macrophages to increase tumor necrosis factor in the macrophage supernatants. This can be detected either in the presence of absence of endotoxin. We have also established the kinetics of such TNF production over a 24 hour period. These data represent the first demonstration of cytokine release due to photodynamic therapy and may explain indirect cytotoxicity of PDT as well as vascular effects. We are continuing investigations of the treatment of patients with endobronchial malignancies with PDT and we have now treated 18 patients with endobronchial disease with PDT. There is a 70% response rate in these patients and the patients are well palliated and photodynamic therapy of the bronchus has now become our preferred method of endobronchial therapy. We are also now performing photodynamic therapy for treatment of pleural malignancies. We have presently treated 7 patients with debulking of pleural malignancies and intraoperative photodynamic therapy. This is now being studied as an approved Phase I trial at the Clinical Center. Before performing these human studies we performed canine experiments in which we established the dose tolerance of normal thoracic tissue (esophagus, lung, heart, chest wall and diaphragm) to PDT.